The proposed research is concerned with the interaction of chemical carcinogens with DNA and the consequence (damage and repair) of this reaction as it relates to the integrity of the cell. Damage and repair to DNA in vivo will be monitored by prelabeling the DNA in partially hepatectomized or newborn animals and analysis on an alkaline sucrose gradient. Repair will be studied in susceptible and non-susceptible tissues. The time relationship between DNA repair and loss of specific alkylated products will be studied by using radioactive carcinogens. The presence or absence of specific alkylated products will be determined at different times following the induction of damage to DNA by a carcinogen. The effect of inhibitors on DNA repair in vivo will be studied. Inhibitors of protein, RNA, and DNA synthesis will be used. A variety of other chemicals will be assayed for inhibition of DNA repair.